AB1108 EFFECT OF GUSELKUMAB ADMINISTERED EVERY 8 WEEKS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS PERSISTS BETWEEN CONSECUTIVE DOSES AND IS DURABLE: POST HOC ANALYSIS OF A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
Authors: P. J. Mease, X. Baraliakos, V. Chandran, E. Soriano, P. Nash, A. Deodhar, E. Rampakakis, N. Shiff, S. D. Chakravarty, M. Shawi, J. F. Merola, I. Mcinnes
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The efficacy of guselkumab (GUS), a fully human IL-23p19 subunit inhibitor, in patients (pts) with active psoriatic arthritis (PsA) has been previously shown across a variety of PsA domains and baseline (BL) pt characteristics<sup>[1-3]</sup>. Given the central role of the IL-23/Th17 pathway in PsA, it has been hypothesized that IL-23 inhibition with GUS may provide persistent and durable clinical responses between doses and over time when administered every 8 weeks (Q8W). <h3>Objectives</h3> To assess at the pt level the persistence of effect of GUS Q8W between doses and its durability of effect over time. <h3>Methods</h3> DISCOVER-2 was a phase 3, randomized, double-blind, placebo (PBO)-controlled study that enrolled pts with active PsA despite standard therapies. Pts were biologic-naïve, had tender and swollen joint counts (TJC/SJC) each ≥5, and C-reactive protein (CRP) ≥0.6 mg/dL. Pts were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO with crossover to GUS 100 mg Q4W at W24. In the current analysis, only pts treated with GUS Q8W (N=248) were included. Persistence of effect between consecutive dosing visits was described with the proportion of pts maintaining response (as defined below) in outcomes assessed during dosing visits (Disease Activity index for PsA [DAPSA], clinical DAPSA [cDAPSA]). Durability of effect was assessed with the Kaplan Meier estimator of the survival function where each pt contributed follow-up from the first time of achievement of clinical response within the 24-week period and the time of loss of response or last available assessment through W100. Definitions of clinical response included achievement of clear/almost clear skin (investigator's global assessment [IGA] 0/1; among pts with BL IGA&gt;1) or minimal clinically important improvements (MCII) in DAPSA (≥7.25), cDAPSA (≥5.7), skin visual analog scale (VAS; ≥15 mm), and PsA Disease Activity Score (PASDAS; ≥0.8). <h3>Results</h3> Between consecutive (Q8W) dosing visits through W52, the proportion of pts maintaining response ranged from 93.3% (DAPSA MCII between W4 and W12) to 99.1% (DAPSA/cDAPSA MCII between W28 and W36), depending on the time interval. Among pts showing clinical response within the first 24 weeks, the estimated mean (SE) duration of maintenance was 58.6 (2.2) weeks for DAPSA MCII, 52.4 (2.0) weeks for cDAPSA MCII, 75.7 (1.6) weeks for. IGA 0/1, 71.7 (1.9) weeks for skin VAS MCII, and 76.7 (1.4) weeks for PASDAS MCII (Figure 1). As estimated probabilities of maintenance of effect at W100 were between 65% (IGA 0/1) and 90% (PASDAS MCII) for all outcomes assessed, median duration of effect could not be calculated. <h3>Conclusion</h3> Treatment with GUS Q8W was associated with long-lasting effects in both joint- and skin-related outcomes, as well as in multi-domain composite outcomes, in individuals with PsA. These results highlight that, in addition to continuous improvement in clinical response rates over time, GUS Q8W provides consistent and highly durable responses between consecutive doses. <h3>References</h3> [1]McInnes IB, et al. <i>Arthritis Rheumatol</i>. 2022;74:475. [2]Ritchlin CT, et al. <i>RMD Open</i>. 2022;8:e002195. [3]Ritchlin CT, et al. <i>Arthritis Rheumatol</i>. 2022;74 (suppl 9). <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Xenofon Baraliakos Speakers bureau: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Biocad, Chugai, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Vinod Chandran Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and Eli Lilly, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Peter Nash Speakers bureau: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Consultant of: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Grant/research support from: UCB, AbbVie, Pfizer, Eli Lilly, Novartis, GlaxoSmithKline, MSD, Samsung, Janssen, Gilead/Galapagos, Boehringer-Ingelheim, Sun, Atul Deodhar Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., Natalie Shiff Shareholder of: AbbVie, Gilead, Iovance, Jazz Pharmaceuticals, Johnson &amp; Johnson, Novavax, and Viatris, Employee of: Janssen Scientific Affairs, LLC, Soumya D Chakravarty Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Pharmaceutical Companies, Joseph F. Merola Consultant of: Amgen, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma, Iain McInnes Shareholder of: Causeway Therapeutics, and Evelo Compugen, Consultant of: AstraZeneca, AbbVie, Bristol Myers Squibb, Amgen, Eli Lilly, Cabaletta, Compugen, GlaxoSmithKline, Gilead, Janssen, Novartis, Pfizer, Sanofi, Roche, and UCB, Grant/research support from: AstraZeneca, Bristol Myers Squibb, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Roche, and UCB.